Breast cancer affects 1 in 7 women during their lifetime, which translates to a 13% lifetime probability of developing the disease. Nearly 220,000 new cases are diagnosed with breast cancer each year; in 75% of these cases, the disease is at early stage (I or II). At these early stages, breast cancer patients can be treated via breast conservation surgery (BCS). Following the initial surgery, up to 40% of the cases result in local recurrence due to inadequate surgical margins with viable cancer cells left at the lumpectomy site (i.e. positive margins). We propose to reduce the 40% recurrence rates caused by inadequate margins in BCS using a novel device that reliably and precisely sterilizes the post-lumpectomy cavity, creating a tumor-free cavity, intraoperatively, via conductive thermal ablation. We have designed, built, and tested a device that enables highly effective conductive thermal ablation in vivo, as shown in the Preliminary Studies of this proposal. Based on these results, we hypothesize that conductive interstitial thermal therapy (CITT) can reliably and precisely induce irreversible thermal damage in targeted tissue to "sterilize" surgical margins after primary tumor resection. Our ultimate goal is that our device will become an intraoperative treatment in BCS to reduce local tumor recurrence resulting from inadequate surgical margins. In this project, our objective is to demonstrate the control and predictability of CITT in creating negative margins and the preclinical efficacy of margin ablation by CITT. To achieve this objective, we will pursue the following specific aims. Specific Aim 1. Demonstrate our ability to control the extent of thermal damage resulting from CITT, in vivo, in a swine model. Specific Aim 2. Demonstrate that CITT can reliably create negative margins, in vivo. Our long-term goal is to develop a new treatment paradigm for same-day diagnosis and first-line treatment of breast cancer by combining surgical resection of malignant tumors with effective, predictable thermal ablation of the margins by CITT; importantly, this modality is safe for both the patient and the surgical team. It can also be applied, through further research, to other types of cancers (e.g. lung, kidney, head and neck) that involve surgical resection of solid tumors. [unreadable] [unreadable] [unreadable]